Related Experiment Video

Updated: Sep 19, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

552

Modulation of podocyte extracellular matrix remodeling in membranous nephropathy by the NFATc3/LRRC55/BK channel

Yaling Guo1,2, Jingliang Min3, Baochao Chang2

  • 1Department of Nephrology The First Affiliated Hospital of Jinan University Guangzhou Guangdong China.

Journal of Cell Communication and Signaling
|June 16, 2025
PubMed

Insights

Nuclear factor of activated T-cells 3 (NFATc3) worsens membranous nephropathy by regulating the LRRC55/BK channel, increasing podocyte injury and extracellular matrix remodeling. Targeting this axis may offer new therapeutic strategies for kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Membranous nephropathy (MN) is a leading cause of nephrotic syndrome.
  • Podocyte injury is central to MN pathogenesis.
  • The LRRC55/BK channel axis is implicated in Ang II-induced podocyte apoptosis.

Purpose of the Study:

  • Investigate the upstream regulation of the LRRC55/BK channel by NFATc3.
  • Elucidate the role of NFATc3 in Ang II-induced podocyte injury and ECM remodeling.
  • Explore the NFATc3/LRRC55/BK axis as a potential therapeutic target in MN.

Main Methods:

  • Ang II-induced podocyte injury model in vitro.
  • NFATc3 overexpression and knockdown studies.
  • RNA sequencing (RNA-seq) for gene expression analysis.
  • Patch-clamp electrophysiology to assess BK channel activity.
  • In vivo studies using mouse models of MN.

Main Results:

  • NFATc3 overexpression increased LRRC55 transcription, BK channel activity, and intracellular calcium, worsening podocyte apoptosis and impairing migration.
  • Significant upregulation of ECM genes, including fibronectin and collagen I, was observed.
  • NFATc3 knockdown attenuated renal injury, proteinuria, and fibrosis in vivo.
  • LRRC55 overexpression or BK channel activation exacerbated podocyte injury and MN progression.

Conclusions:

  • NFATc3 aggravates Ang II-induced podocyte injury via transcriptional regulation of LRRC55 and BK channel activation.
  • This pathway contributes to ECM remodeling and glomerular dysfunction in MN.
  • The NFATc3/LRRC55/BK axis represents a promising therapeutic target for MN treatment.
Keywords:
BK channelLRRC55NFATc3extracellular matrix remodelingmembranous nephropathypodocyte injury

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